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“Cancer Analogy”

Riyadh Microbiology/Infectious Disease Club Meeting. “Cancer Analogy”. Hail M. Al-Abdely, MD Section of Infectious Diseases Department of Medicine King Faisal Specialist Hospital & Research Centre. History. 2 Nov 1999

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“Cancer Analogy”

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  1. Riyadh Microbiology/Infectious Disease Club Meeting “Cancer Analogy” Hail M. Al-Abdely, MDSection of Infectious DiseasesDepartment of MedicineKing Faisal Specialist Hospital & Research Centre

  2. History • 2 Nov 1999 • 13 y/o Male previously healthy referred from Dahran Health Center with a 3-months h/o generalized weakness & wt loss. RUQ pain. • CT abd revealed multiple hepatic lesions and mediastinal lymphadenopathy

  3. Course at KFSH • Chronically ill. No fever • Hepatomegaly • WBC 8.25 with 35% eosinophils • Fundoscopy: • Multiple retinal lesions

  4. Possible Diagnoses??

  5. FNA from the liver showed fungal hyphae • Culture was negative • Treated with ABLC and itraconazole for 4 weeks with no response

  6. Course • FNA from liver • Mediastinal lymph node bx

  7. What Fungus?

  8. Cladophialophora bantiana

  9. Course • Therapy • Liposomal AmB 7.5mg/kg/day (Stopped 7 May 2000) • Itraconazole 200mg Q12hrs • Improved clinically and radiologically

  10. 15 Jan 2000

  11. 29 Dec 2001 1 July 2000

  12. Course • 30 June 2002 • C/O nausea and vomiting and coordination impairment • Irregular on itraconazole for 2 months

  13. 2 July 2002

  14. 8 July 2002

  15. 8 July 2002

  16. Course • Treated with i.v itraconazole 250mg Q12 hrs • Discharged (30 July 2002) on liquid itraconazole 300 mg BID • Improved

  17. Course • 27 Aug 02 • Nausea , vomiting, bilateral weakness and discoordination • MRI brain worse but CT chest better • Therapy • i.v itraconazole • i.v 5-FC • i.v liposomal AmB

  18. 28 Sep 2002

  19. What to do?

  20. Course • Voriconazole 200mg i.v Q12 hrs for 3 weeks followed by po. • Remarkable improvement and discharged • Seen in clinic 11 Nov 2002 • Excellent condition; walking independently and no coordination problems and gained several Kgs

  21. 11 Nov 02

  22. Course • 19 Feb 2003 • Acute confusion, weakness

  23. 19 Feb 2003

  24. Ventriculoscopy

  25. Course • Therapy • i.v voriconazole • i.v liposomal AmB • i.v Caspofungin • Intra-ventricular Ampho B • Intra-ventricular 5-FC

  26. 2 Apr 03

  27. Course • Nothing helped and the patients died on 13 April 2003 after 3 years of “palliative” therapy for disseminated Cladophialophora bantiana • Extensive immunological workup was negative

  28. CID 2004:38 (15 January)

  29. Revankar, et al. CID 39:206. 2004 101 cases • Cladophialophora bantiana accounted for 48 (48%) • Ramichloridium mackenzei, seen in 13 (13%) • Ochroconis gallopavum, seen in 5 (5%)

  30. Continue,

  31. Medical Therapy • Current agents • AmB: typically resistant • Lipid AmB: limited experience • 5-FC: Good in-vitro and in few cases with surgery • Itraconazole: good in vitro • Voriconazole: limited data. 2 cases of failure • Caspofungin: Resistant in vitro. No clinical data • Future • Data only with posaconazole • In vitro and animal

  32. Future Therapy • Posaconazole against C. bantiana in mice • Mice infected either intravenously or intracranially with C. bantiana • Mice treated with posaconazole compare with other antifungals AAC 2005 (In press)

  33. Survival of immunosuppressed ICR mice infected with C. bantiana intravenously and treated with amphotericin B (AMB) 3 mg/kg/day, itraconazole 30 mg/kg three times daily and posaconazole 30 mg/kg/day for 7 days.

  34. Fungal burden (panel B) of immunosuppressed ICR mice infected with C. bantiana intravenously and treated with amphotericin B (AMB) 3 mg/kg/day, itraconazole 30 mg/kg three times daily and posaconazole 30 mg/kg/day for 7 days.

  35. Survival of BALB/c mice infected with C. bantiana intracranially and treated with posaconazole at a dose of 5, 15, 25, or 50 mg/kg/day for 28 days 2 starting at day one post infection.

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